After seven years of development, NuPathe Inc. finally received a green light from the FDA for its sumatriptan patch, branded Zecuity (sumatriptan iontophoretic transdermal system), for the acute treatment of migraine with or without aura in adults.

The single-use, battery-powered patch, formerly known as Zelrix, is designed to deliver sumatriptan when applied to the upper arm or thigh during a migraine.

Phase III studies that enrolled 800 patients using more than 10,000 Zecuity patches demonstrated relief of headache pain, migraine-related nausea (MRN) and sensitivity to light and sound, with a low rate of triptan sensations such as chest tightness and flushing.

Zecuity's approval was disclosed after Thursday's market close, and the company's shares (NASDAQ:PATH) gained nearly 19 percent in early trading on Friday. The stock lost steam as the day progressed, however, closing at $3.30, down a penny. Trading was more than 25 times the stock's average daily volume.

Conshohocken, Pa.-based NuPathe slashed overhead and delayed CMC activities, including manufacturing of commercial supplies, to conserve cash following a complete response letter (CRL) from the FDA in August 2011 over questions about the patch's battery-operated components and coating material. The company resubmitted its new drug application (NDA) in July 2012. (See BioWorld Today, Aug. 31, 2011.)

Although Zecuity was approved through the 50b(b)(2) pathway, NuPathe CEO Armando Anido told BioWorld Today the company is "very happy" with the label, which blends data from sumatriptan with NuPathe's own clinical data on Zecuity, the first FDA-approved migraine patch.

"Having our clinical data in there is very important to us, because we offer a product that bypasses the GI tract," said Anido, who joined NuPathe in July 2012 after six years heading Auxilium Pharmaceuticals Inc. "For the vast majority of patients who have migraine-related nausea along with their migraine headache pain, this is a great alternative."

In the pivotal study, twice as many patients treated with Zecuity achieved freedom from headache pain at two hours compared with placebo, but those numbers were just 18 percent and 9 percent, respectively. However, the effect was greater on reduced headache pain, with 53 percent of Zecuity patients reporting relief compared to 29 percent on placebo. In addition, 84 percent were free from MRN at two hours compared to 63 percent on placebo.

All along, NuPathe cited MRN as a major driver for a non-oral migraine product and a key product differentiator. Of approximately 16 million U.S. migraine patients who are diagnosed and treated, nearly half experience MRN in at least half of their migraine attacks, according to the company.

NuPathe now turns its attention to partnering discussions and commercial ramp-up. The company will begin to produce validation batches, scale-up device manufacturing and generate launch supplies, with plans to begin shipping product in the fourth quarter, Anido said.

The company is talking with "large, medium and small companies that are very interested in the migraine space" about potential partnerships, he added. NuPathe is flexible on whether to market Zecuity on its own in the U.S. or to co-promote. Globally, the company is seeking one or more partners that can offer regulatory and commercial expertise in targeted markets, especially Europe, Japan, Southeast Asia and South America.

NuPathe's pre-launch planning included market research with more than 700 physicians, more than 800 patients and pharmacy and medical directors from U.S. insurers accounting for more than 130 million covered lives. The company also developed a detailed field sales launch plan targeting 10,000 neurologists and headache specialists who account for approximately one-third of U.S. triptan prescribing volume and 30,000 primary care providers who account for another third.

The company plans to postpone a pricing decision until the commercialization strategy is set, although "we think premium pricing for this product is appropriate," Anido said. Although generic formulations of sumatriptan are available, managed care companies are comparing Zecuity to GlaxoSmithKline plc's injectable Imitrex at approximately $95 per dose, according to Anido, "so somewhere in that range is where we'll probably end up." he said.

The company agreed to conduct three pediatric post-marketing studies in 12- to 17-year-olds. The company plans to initiate the first, a pharmacokinetics study, this year. A second, randomized, double-blind, placebo-controlled, single-dose efficacy and safety study will likely begin next year, Anido said, followed by a 12-month open-label safety study.

The FDA also requested a seven-day, repeat-dose rodent dermal study and, depending on those results, a follow-up rodent dermal carcinogenicity study.

NuPathe will need additional capital prior to launch, Anido conceded, though the scope and shape of a financing will be dictated by partnering terms. The company reported $1.3 million in cash and equivalents as of Sept. 30, 2012, but a $28 million financing in October 2012, together with a restructuring of outstanding debt, should see it into the fourth quarter.

Even with a small slice of the lucrative migraine market, Zecuity could generate attractive sales. In a research report, Leerink Swann LLC analyst Michael Schmidt projected peak U.S. sales potential of approximately $400 million in 2027, when patent protection expires. He also valued NuPathe at $6 per share, representing a $200 million market cap. A return to that price range would be welcome news for investors. The stock's historic high, $10.22, was reached the day the company completed its initial public offering in August 2010. In the past year, shares generally have traded at less than half that value. (See BioWorld Today, Aug. 9, 2010.)

The Zecuity approval was a bit of a downer for MAP Pharmaceuticals, which is developing Levadex, an orally inhaled formulation of the intravenous drug dihydroergotamine, in acute migraine. Levadex also received a CRL last year related to chemistry, manufacturing and controls and to issues related to a facility inspection at a third-party manufacturer. The company resubmitted the NDA in October. (See BioWorld Today, March 28, 2012.)

On Friday, shares of MAP (NASDAQ:MAPP) lost 13 cents, closing at $15.58.